What Is Charcot Marie Tooth Disease

Overview

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN), is an inherited disorder affecting the peripheral nerves. It leads to various symptoms in the arms and legs, such as muscle weakness, wasting, and diminished sensation. CMT is a progressive condition, meaning that its symptoms tend to worsen over time. 

CMT is characterized by problems with the peripheral nerves, which connect the central nervous system (the brain and spinal cord) to the rest of the body. These nerves transmit messages from the brain and spinal cord to the muscles and other areas in the body, as well as relaying  information from these areas back to the brain. When these nerves are affected, as is the case in CMT, it is referred to as peripheral neuropathy. 

The disease was named after the physicians who first identified it in 1886: Jean-Martin Charcot, Pierre Marie, and Henry Tooth. While there is currently no cure for CMT, there are available treatments to help manage its symptoms.

Types of CMT

Due to the involvement of multiple genes and the wide variation in symptoms among different types, the classification of Charcot-Marie-Tooth disease (CMT) is complex. Some research suggests the need for a new classification system, but this is still a topic of debate.¹ 

Here are the key details about the main types of CMT: 

CMT1: 

It is caused by issues with the protective myelin sheath of the nerves. Symptoms typically begin before the age of 20, and life expectancy is usually unaffected. The most common subtype, CMT1A, results from problems with a protein called PMP22. It progresses slowly and primarily affects the lower legs. There are six other subtypes caused by different genes. 

CMT2: 

It occurs due to problems with the axons in peripheral nerve cells. Compared to CMT1, individuals with CMT2 may experience less sensory loss. The age of onset varies, but it is often diagnosed by the age of 25. Over a dozen subtypes exist, each caused by different genes, and certain subtypes can lead to breathing or speaking difficulties. 

CMT3 (Dejerine-sottas disease): 

This rare form of CMT causes severe muscle and sensory symptoms in infants. It can have multiple genetic causes.

CMT4: 

This type of CMT is inherited recessively, requiring the inheritance of  the problem gene from both parents to develop it. There are several subtypes caused by different genes, but it is not commonly diagnosed in the United States.

CMTX1: 

It arises from a gene problem on the X chromosome, affecting the cells responsible for producing the myelin sheath of nerve cells. Symptoms are usually more severe in individuals with XY chromosomes (male sex) than those with XX chromosomes (female sex).

Congenital hypomyelinating neuropathy: 

It is a severe form of CMT typically diagnosed in young infants. 

Causes of CMT

CMT is a congenital disease that is present from birth, although its symptoms typically manifest during adolescence or adulthood. 

The condition arises from genetic issues, where one or more mutated genes are involved. In most cases, these problem genes are inherited from one or both parents, and individuals can pass them on to their own children. 

In rare instances, individuals are born with spontaneous gene mutations that cause CMT, without inheriting them from their parents. These individuals will develop CMT and can also transmit the CMT-causing genes to their offspring. 

The genes associated with CMT can affect different components of the peripheral nerves. The most common impact is on the myelin sheath, the protective coating of the nerves. In other cases, the condition affects the axon, the  part of the nerve cell that connects it with other nerve cells to transmit information. Some types of CMT affect both the axon and the myelin sheath. These changes impede the efficient transmission of signals between the central nervous system and the rest of the body through the peripheral nerves. 

Since there are various types of CMT, each with a distinct genetic cause, seeking guidance from a genetic counselor can be beneficial for individuals diagnosed with CMT or their families. A genetic counselor can provide insights into the familial risk of CMT and offer guidance accordingly.

Signs and symptoms of CMT

Symptoms of CMT can emerge during adolescence or even as late as mid-adulthood.²

Early indications include:

• Clumsiness, stumbling, or tripping
• Difficulty walking or running
• Falls 

As the condition progresses, symptoms may involve: 

• Weakness in leg or arm muscles
• Reduced or absent reflexes (areflexia)
• High-stepping or foot drop while walking
• Weakness in hands, affecting handwriting or fastening clothes
• Muscle atrophy
• Stiff joints (joint contracture)
• Muscle pain
• Cramping
• Balance problems
• Decreased sensation, such as reduced ability to feel pain, heat, or cold
• Fatigue
• Nerve pain
• Hearing loss 

Physical manifestations of CMT can include:

• Foot issues like hammer toes high arches, or flat feet
• Muscle loss in the lower leg, resulting in a distinct curved calf shape
• Scoliosis

Symptoms typically affect both sides of the body. As CMT advances, voluntary movements can become challenging. This can impact fine motor skills, mobility and in some cases, speech, swallowing, or breathing. While CMT symptoms can vary among individuals, muscle weakness, wasting in the limbs, reduced reflexes, and skeletal changes are common outcomes. Mild to moderate loss of limb sensation is also frequently observed. Various treatments, therapies, and supportive devices are available to manage most symptoms of CMT. 

Management and treatment for CMT

Currently, there is no known cure for CMT, and its progression is typically slow. No treatment has been proven to halt the progression of the disease either so the he focus of treatment is on managing symptoms to enhance quality of life.³

Physical therapy:

Physical therapy is a common approach for individuals with CMT. A physical therapist can create a personalized physical therapy plan. This therapy can help alleviate pain and fatigue while maintaining range of motion, flexibility, muscle strength, balance, and fine motor skills. Stretching, strength training, and aerobic exercises may be recommended. It is important to consult with a doctor before making significant changes to physical activity levels.

Assistive devices:

Various assistive devices can be beneficial for people with CMT, including splints or braces to enhance comfort and stability during daily tasks, walkers or wheelchairs to improve mobility, hearing aids for hearing loss, and orthotic shoes to address physical changes in the feet. An occupational therapist can provide guidance on the use of assistive devices and offer strategies for daily living.

Medication:

If necessary, medications can be prescribed by a doctor to alleviate symptoms such as pain and cramping.

Surgery:

Orthopedic surgery may be considered for certain individuals with CMT to address foot or joint problems.

Diagnosis of CMT

To diagnose CMT, your doctor will inquire about your symptoms, medical history, and family medical conditions. They will conduct a physical and neurological examination to assess reflexes, coordination, and muscle strength.

Additional tests may be requested to evaluate potential nerve damage, including:

Nerve conduction study (NCV): Measures the speed of electrical signals in peripheral nerves using electrodes placed on the skin.

Electromyography (EMG): Measures electrical activity in muscles using small needles inserted into a muscle while you contract and relax it.

Nerve biopsy: Involves removing a small nerve sample, typically from the calf, for  analysis under a microscope to detect CMT signs.

Genetic testing: Involves a blood test to identify genetic mutations associated with CMT.

Risk factors

The primary risk factor for Charcot-Marie-Tooth disease (CMT) is having a family history of the condition. CMT is typically inherited in an autosomal dominant or autosomal recessive pattern, which means that individuals with a parent or parents who have CMT are at a higher risk of developing the condition themselves.

Complications

Complications of CMT include:

• Muscle weakness and atrophy
• Foot deformities
• Hand and arm weakness
• Sensory impairments
• Balance and coordination problems
• Skeletal abnormalities: In some cases, CMT can cause skeletal changes such as scoliosis (curvature of the spine) or joint contractures (stiffness and immobility of joints)
• Breathing and swallowing difficulties
• Emotional and psychological impact

FAQs

How can I prevent CMT?

Charcot-Marie-Tooth disease (CMT) is a genetic condition, and currently, there is no known way to prevent it. CMT is caused by inherited gene mutations, and these mutations cannot be prevented or reversed.

How common is CMT?

Charcot-Marie-Tooth disease (CMT) is considered to be one of the most common inherited neurological disorders worldwide andit is estimated that CMT affects approximately 1 in 2,500 individuals.⁴

When should I see a doctor?

If you are experiencing the symptoms mentioned above and you suspect that you have CMT, schedule an appointment with your GP.

Summary

Charcot-Marie-Tooth disease (CMT) is an inherited disorder that affects the peripheral nerves, leading to muscle weakness, wasting, and diminished sensation in the arms and legs. It is a progressive condition with symptoms worsening over time. CMT is caused by genetic mutations and currently has no known cure. 

Treatment focuses on managing symptoms through physical therapy, assistive devices, medication, and surgery. 

Diagnosis involves a physical and neurological examination, as well as tests such as nerve conduction studies, electromyography, nerve biopsy, and genetic testing. CMT is relatively common, affecting approximately 1 in 2,500 individuals.